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All preclinical procedures for analgesic drug discovery involve two components: 1) a "pain stimulus" (the principal independent variable), which is delivered to an experimental subject with the intention of producing a pain state; and 2) a "pain behavior" (the principal dependent variable), which is measured as evidence of that pain state. Candidate analgesics are then evaluated for their effectiveness to reduce the pain behavior, and results are used to prioritize drugs for advancement to clinical testing. This review describes a taxonomy of preclinical procedures organized into an "antinociception matrix" by reference to their types of pain stimulus (noxious, inflammatory, neuropathic, disease related) and pain behavior (unconditioned, classically conditioned, operant conditioned). Particular emphasis is devoted to pain behaviors and the behavioral principals that govern their expression, pharmacological modulation, and preclinical-to-clinical translation. Strengths and weaknesses are compared and contrasted for procedures using each type of behavioral outcome measure, and the following four recommendations are offered to promote strategic use of these procedures for preclinical-to-clinical analgesic drug testing. First, attend to the degree of homology between preclinical and clinical outcome measures, and use preclinical procedures with behavioral outcome measures homologous to clinically relevant outcomes in humans. Second, use combinations of preclinical procedures with complementary strengths and weaknesses to optimize both sensitivity and selectivity of preclinical testing. Third, take advantage of failed clinical translation to identify drugs that can be back-translated preclinically as active negative controls. Finally, increase precision of procedure labels by indicating both the pain stimulus and the pain behavior in naming preclinical procedures.
Learn More >The reason why some individuals develop chronic symptoms, whiplash-associated disorder, following whiplash trauma is poorly understood. We explored whether precollision pain-related diagnoses, medically unexplained symptoms, and psychiatric diagnoses are related to whiplash-associated disorder.
Learn More >To understand the efficacy of zolmitriptan applied with Adhesive Dermally Applied Microarray (ADAM) in treating types of migraine (those with severe headache pain, the presence of nausea, treatment ≥2 hours after migraine onset, or migraine present upon awakening) that are historically considered to be less responsive to oral medications.
Learn More >To investigate differences in clinical, psychological and psychophysical outcomes according to use of prophylactic medication (amitriptyline) in tension type headache (TTH).
Learn More >Several small studies have suggested that spinal manipulation may be an effective treatment for reducing migraine pain and disability. We performed a systematic review and meta-analysis of published randomized clinical trials (RCTs) to evaluate the evidence regarding spinal manipulation as an alternative or integrative therapy in reducing migraine pain and disability.
Learn More >Peripheral nerve stimulation is the direct electrical stimulation of named nerves outside the central neuraxis to alleviate pain in the distribution of the targeted peripheral nerve. These treatments have shown efficacy in treating a variety of neuropathic, musculoskeletal, and visceral refractory pain pathologies; although not first line, these therapies are an important part of the treatment repertoire for chronic pain. With careful patient selection and judicious choice of stimulation technique, excellent results can be achieved for a variety of pain etiologies and distributions. This article reviews current and past practices of peripheral nerve stimulation and upcoming advancements in the field.
Learn More >Pain management is complex regardless of whether the pain is acute or chronic in nature or non-cancer or cancer related. In addition, relatively few pain pharmacotherapy options with adequate efficacy and safety data currently exist. Consequently, interest in the role of NMDA receptor antagonists as a pharmacological pain management strategy has surfaced. This narrative review provides an overview of the NMDA receptor and elaborates on the pharmacotherapeutic profile and pain management literature findings for the following NMDA receptor antagonists: ketamine, memantine, dextromethorphan, and magnesium. The literature on this topic is characterized by small studies, many of which exhibit methodological flaws. To date, ketamine is the most studied NMDA receptor antagonist for both acute and chronic pain management. Although further research about NMDA receptor antagonists for analgesia is needed and the optimal dosage/administration regimens for these drugs have yet to be determined, ketamine appears to hold the most promise and may be of particular value in the perioperative pain management realm.
Learn More >A national crisis of opioid-related morbidity, mortality, and misuse has led to initiatives to address the appropriate role of opioids to treat pain. Deployment of a guideline from the Centers for Disease Control and Prevention to reduce the risks of opioid therapy has raised substantial clinical and public policy challenges. The agency anticipated implementation challenges and committed to reevaluating the guideline for intended and unintended effects on clinician and patient outcomes.
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